The K-562 cell line, originally established at our laboratory, has the potential for spontaneous and/or induced differentiation into one or more hematopoietic progenitor cells. The capacity for cell renewals, the ability to give rise to progenitors of five hematopoietic cell lineages, high plating efficiency in semisolid media and antigenic expression are consistent with the characteristics of stem cells. We have found that K-562 cells are endowed with various antigens found in bone marrow and peripheral blood cells. The expression of these cell surface antigens was demonstrated with a variety of monoclonal antibodies. Different sublines derived from the original line were found to have different proportions of hematopoietic progenitor cell antigens. It is possible that the original cultures contained a mixture of stem cells, committed progenitors and precursors of various hematopoietic cells and that a selection of one of these populations occurred during prolonged in vitro culture. Thus, results obtained with different sublines may explain the discrepancies reported on the nature of the K-562 cells. The original K-562 cell line appears to be more sensitive than some of the sublines to most of the different ones tested. This response may be due to the presence of a greater proportion of pluripotent stem cells in the original cell line. The specific aims of the research in progress are: (1)\to study the spontaneous and induced differentiation of various sublines of K-562 cells; (2)\to investigate the ultrastructure and cytochemical changes associated with differentiation; (3)\to assess if the K-562 cells lose their characteristic "malignancy" at some stage of differentiation; (4)\to correlate the chromosomal evolution of K-562 cells with their capacity for cell differentiation; and (5)\to determine whether or not the K-562 sublines with specific chromosome markers can differentiate to one or more types of mature cell lines.